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Freedom from ototoxicity in aminoglycoside treated neonates: a mistaken notion
Abstract:
Pediatricians commonly consider aminoglycoside antibiotics to be less ototoxic in neonates than in adults. This concept is based on the results of pure tone audiometry performed in children treated with aminoglycosides during the neonatal period. However, conflicting results were obtained when using brain stem response audiometry (BSRA) in a group of 26 aminoglycoside treated neonates and a control group of 20 treated neonates during their stays in intensive care units (mean gestational age: 34.6 weeks). Latencies of wave V significantly differed between the two groups indicating hearing alterations in the treated group. A statistical correlation was demonstrated between initial and final values of wave V and the total doses of antibiotic administered per kilogram of body weight (p less than 0.01). Most neonates were premature with an immature hearing apparatus. To demonstrate the effect of aminoglycosides on the developing organ of Corti, neonate kittens were chosen as animal models--the onset of hearing occurs 10 days after birth. BSRA was performed every 3 days from birth for 20 days and thereafter every 6 days for the following 30 days. Five kittens treated with a low dose of gentamicin for 20 days were compared with a control group of 5 untreated kittens from the same litters and a group of 5 adult cats receiving the same antibiotic therapy. On the 50th day, all animals were sacrificed and their cochleas were prepared for electron microscopic evaluation. No ultrastructural modifications or BSRA alterations were noted in the adult group. The untreated kittens exhibited a normal pattern of BSRA maturation and their organs of Corti appeared normal. On the contrary, evidence of abnormal hearing maturation and of anatomical damage in the outer hair cells of the first coil of the cochlea was found in the treated kittens. Laboratory findings corroborate our clinical findings that aminoglycoside antibiotics are more ototoxic in neonates than in adult cats.